Rab 23 is expressed in the glomerulus and plays a role in the development of focal segmental glomerulosclerosis.
BACKGROUND
Rab23, a member of the Rab family of small GTPase, has a function in antagonizing sonic hedgehog signal transduction. Both Rab-family and hedgehog-related proteins are involved in sclerosis and fibrosis in certain pathological states, but their roles in focal segmental glomerulosclerosis (FSGS) remain unclear.


METHODS
The FSGS model was established in Balb/c mice by a single injection of adriamycin. Serum, urine and mice kidneys were collected on Days 0, 7, 15 and 20. Western blot analysis was performed to detect the levels of Rab23 in the samples. Immunohistochemistry was used to examine the expressional profiles of Rab23 in kidneys. The expressions of transcripts of Rab23, extracellular matrix (ECM) proteins, and various hedgehog signalling pathway genes in kidneys or mesangial cells were evaluated by real-time RT-PCR. The effect of Rab23 on ECM protein expressions was evaluated by the knockdown or overexpression of Rab23 in mesangial cells.


RESULTS
Our results show that elevations of Rab23 were observed in the urine, but not in the serum, of the FSGS mice. Rab23 and hedgehog signalling pathway genes were constitutively expressed in normal kidneys and were significantly up-regulated in the kidneys of FSGS mice. The basal expression of Rab23 was identified in glomeruli, and mesangial cells displayed obvious elevation of Rab23 in the FSGS state. The knockdown or overexpression of Rab23 affected the collagen expression in cultured mesangial cells.


CONCLUSIONS
An autocrine loop of hedgehog signalling could be activated in mesangial cells in the FSGS state, and Rab23 may be elevated to suppress hedgehog signalling and/or influence collagen synthesis. Importantly, Rab23 could serve as a biomarker that indicates the severity of FSGS.
Huang
Tzu-Hao
TH
Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
Shui
Hao-Ai
HA
Ka
Shuk-Man
SM
Tang
Bor-Luen
BL
Chao
Tai-Kuang
TK
Chen
Jin-Shuen
JS
Lin
Yuh-Feng
YF
Chen
Ann
A
D000818:Animals; D001806:Blood Urea Nitrogen; D004195:Disease Models, Animal; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D053823:Hedgehog Proteins; D012333:RNA, Messenger; C431746:Rab23 protein, mouse; D020691:rab GTP-Binding Proteins